Abstract:
:New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure-activity relationships, along with the comparative molecular dynamics simulations within the eukaryotic rRNA decoding site, showed high sensitivity of 6'-position to substitution, indicating that the rational design of potent stop-codon read-through inducers requires consideration of not only the structure and energetics of the drug-RNA interaction but also the dynamics associated with that interaction.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Sabbavarapu NM,Pieńko T,Zalman BH,Trylska J,Baasov Tdoi
10.1039/c8md00001hsubject
Has Abstractpub_date
2018-02-02 00:00:00pages
503-508issue
3eissn
2040-2503issn
2040-2511pii
c8md00001hjournal_volume
9pub_type
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